イノシン酸

関: IMP、inosinate、inosine monophosphate

WordNet

street name for lysergic acid diethylamide (同)back breaker, battery-acid, dose, dot, Elvis, loony toons, Lucy in the sky with diamonds, pane, superman, window pane, Zen
any of various water-soluble compounds having a sour taste and capable of turning litmus red and reacting with a base to form a salt
having the characteristics of an acid; "an acid reaction"

PrepTutorEJDIC

酸性の / 酸味のある,すっぱい(sour) / (言葉・態度などが)厳しい,しんらつな / 酸 / すっぱいもの / 《俗》=LSD

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/12 18:48:25」(JST)

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[Wiki en表示]

Inosinic acid or inosine monophosphate (IMP) is a nucleoside monophosphate. Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine. It is formed by the deamination of adenosine monophosphate, and is hydrolysed from inosine. IMP is an intermediate ribonucleoside monophosphate in purine metabolism. The enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase, encoded by YJR069C in Saccharomyces cerevisiae and containing (d)ITPase and (d)XTPase activities, hydrolyzes inosine triphosphate (ITP) releasing pyrophosphate and IMP.^[1]

Important derivatives of inosinic acid include purine nucleotides found in nucleic acids and adenosine triphosphate, which is used to store chemical energy in muscle and other tissues.

In the food industry, inosinic acid and its salts such as disodium inosinate are used as flavor enhancers.

Inosinate synthesis

The inosinate synthesis is complex, beginning with a 5-phosphoribosyl-1-pyrophosphate (PRPP). In the first step, an amino group given by glutamine is attached at carbon 1 of PRPP. The resulting molecule is 5-phosphoribosylamine, which is highly unstable, with a half-life of 30 seconds at physiologic pH. 5-Phosphoribosylamine gains an amino acid (glycine), becoming glycinamide ribonucleotide (GAR). Then, N10-formyltetrahydrofolate (tetrahydrofolate) transfers a formyl group to glycinamide ribonucleotide to form formyl glycinamide ribonucleotide (FGAR).

This figure shows the pathway described: IMP synthesis.

Using an ATP molecule, glutamine donates an ammonia^{[dubious – discuss]} molecule which is added to the compound forming formylglycinamidine ribonucleotide. Another ATP molecule causes an intermolecular reaction that produces an imidazole ring (5-aminoimidazole ribonucleotide).

The next step of the pathway is adding bicarbonate to make carboxyaminoimidazole ribonucleotide by using ATP (it only happens in fungi and bacteria; high eukaryotes simply add CO2 to form the ribonucleotide). Then, the imidazole’s carboxylate group phosphatises and adds aspartate.

This six-step process links glycine, formate, bicarbonate, glutamine, and aspartate to lead to an intermediate that contains almost all the required atoms to synthesize a purine ring. This intermediate removes fumarate, and a second formyl group from THF is added. The compound gets cycled and forms inosinate^{[dubious – discuss]} after a sort of intermolecular reactions. Inosinate is the first intermediate in this synthesis pathway to have a whole purine ring.

Enzymes taking part in IMP synthesis constitute a multienzyme complex in the cell. Evidences demonstrate that there are multifunctional enzymes, and some of them catalyze non-sequential steps in the pathway.

Adenylate (AMP) and guanylate (GMP) come from inosinate

Within a few steps inosinate becomes AMP or GMP. Both compounds are RNA nucleotides. AMP differs from inosinate by the replacement of IMP's carbon-6 carbonyl with an amino group. The interconversion of AMP and IMP occurs as part of the purine nucleotide cycle.^[2] GMP is formed by the inosinate oxidation to xanthylate (XMP), and afterwards adds an amino group on carbon 2. Hydrogen acceptor on inosinate oxidation is NAD+. Finally, carbon 2 gains the amino group by spending an ATP molecule (which becomes AMP+2Pi). While AMP synthesis requires GTP, GMP synthesis uses ATP. That difference offers an important regulation possibility.

Glutamine-PRPP-amidotransferase

Inosinate takes part in the regulation of purine nucleotides biosynthesis

Inosinate and many other molecules inhibit the synthesis of 5-phosphorybosilamine from 5-phosphoribosyl-1-pyrophosphate (PRPP), disabling the enzyme that catalyzes the reaction: glutamine-5-phosphoribosyl-1-pyrophosphate-amidotransferase. In other words, when levels of inosinate are high, glutamine-5-phosphoribosyl-1-pyrophosphate-amidotransferase is inhibited, and, as a consequence, inosinate levels decrease. Also, as a result, adenylate and guanylate are not produced, which means that RNA synthesis cannot be completed because of the lack of these two important RNA nucleotides.

Applications

Inosinic acid can be converted into various salts including disodium inosinate (E631), dipotassium inosinate (E632), and dicalcium inosinate (E633). These three compounds are used as flavor enhancers with a comparatively high effectiveness. They are mostly used in soups, sauces, and seasonings for the intensification and balance of meat taste.

References

^ Davies O, Mendes P, Smallbone K, Malys N (2012). "Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism". BMB Reports 45 (4): 259–64. doi:10.5483/BMBRep.2012.45.4.259. PMID 22531138.
^ Voet, D, Voet, J. G., Biochemistry (3rd Edition), John Wiley & Sons, Inc., 2004, pg 1095

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English Journal

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SUMMARY There is an alarming rate of human African trypanosomiasis recrudescence in many parts of sub-Saharan Africa. Yet, the disease has no successful chemotherapy. Trypanosoma lacks the enzymatic machinery for the de novo synthesis of purine nucleotides, and is critically dependent on salvage mec
PMID 23369253

Novel inhibitors of inosine monophosphate dehydrogenase in patent literature of the last decade.

Petrelli R, Vita P, Torquati I, Felczak K, Wilson DJ, Franchetti P, Cappellacci L.SourceSchool of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy. riccardo.petrelli@unicam.it.
Recent patents on anti-cancer drug discovery.Recent Pat Anticancer Drug Discov.2013 May 1;8(2):103-25.
Inosine monophosphate dehydrogenase (IMPDH), an NAD-dependent enzyme that controls de novo synthesis of guanine nucleotides, has received considerable interest in recent years as an important target enzyme, not only for the discovery of anticancer drugs, but also for antiviral, antiparasitic, and im
PMID 23016672

S-bacillithiolation protects conserved and essential proteins against hypochlorite stress in firmicutes bacteria.

Chi BK, Roberts AA, Huyen TT, Bäsell K, Becher D, Albrecht D, Hamilton CJ, Antelmann H.Source1 Institute for Microbiology, Ernst-Moritz-Arndt-University of Greifswald , Greifswald, Germany .
Antioxidants & redox signaling.Antioxid Redox Signal.2013 Apr 10;18(11):1273-95. doi: 10.1089/ars.2012.4686. Epub 2012 Oct 18.
Abstract Aims: Protein S-bacillithiolations are mixed disulfides between protein thiols and the bacillithiol (BSH) redox buffer that occur in response to NaOCl in Bacillus subtilis. We used BSH-specific immunoblots, shotgun liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis and r
PMID 22938038

Japanese Journal

2Ep12 TPPリボスイッチを用いた新規アプタマーの合理的設計(タンパク質工学/核酸工学/ペプチド工学,一般講演)

徳井美里,山内隆寛,三好大輔,西村顕,杉本直己
日本生物工学会大会講演要旨集 (63), 147, 2011-08-25
NAID 110008911392

素材レポートうま味素材・まぐろアンセリンEXPの抗疲労機能について(コラーゲンペブチド、イノシン酸含有)

倉重(岩崎) 恵子,譲原一雄
食品と開発 46(6), 69-72, 2011-06
NAID 40018875689

Related Pictures

★リンクテーブル★

リンク元	「6-メルカプトプリン」「イノシン酸」「inosinate」

「6-メルカプトプリン」

Inosinic acid
Names
	IUPAC name 5'-Inosinic acid
	Other names IMP,; Hypoxanthine ribotide
Identifiers
CAS Number	131-99-7
ChEBI	CHEBI:17202
ChEMBL	ChEMBL1233478
ChemSpider	8264
IUPHAR/BPS	5124
Jmol 3D model	Interactive image
MeSH	Inosine+monophosphate
PubChem	8582
	InChI InChI=1S/C10H13N4O8P/c15-6-4(1-21-23(18,19)20)22-10(7(6)16)14-3-13-5-8(14)11-2-12-9(5)17/h2-4,6-7,10,15-16H,1H2,(H,11,12,17)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1 Key: GRSZFWQUAKGDAV-KQYNXXCUSA-N ; InChI=1/C10H13N4O8P/c15-6-4(1-21-23(18,19)20)22-10(7(6)16)14-3-13-5-8(14)11-2-12-9(5)17/h2-4,6-7,10,15-16H,1H2,(H,11,12,17)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1 Key: GRSZFWQUAKGDAV-KQYNXXCUBU ;
	SMILES O=C3/N=C\Nc1c3ncn1[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)COP(=O)(O)O ;
Properties
Chemical formula	C10H13N4O8P
Molar mass	348.21 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	verify (what is ?)
	Infobox references

　　[★]

英: 6-mercaptopurine, mercaptopunne
ラ: 6-mercaptopurinum
同: 6-MP
商: ロイケリン
関: アザチオプリン、制癌薬

GOO. 134-138,1347f
プリン代謝拮抗薬
抗悪性腫瘍薬

白血病治療薬

プリンの6位にSが付加された物質。

代謝

投与された6-MPはPPRP(phosphoribosylpyrophosphateにより6-thioinosine 5'-monophosphate(TIMP)となる
6-thioinosine 5'-monophosphateはいくつかの代謝を経て6-thioguanosine 5'-monophosphate(TGN)となる

作用機序

TIMPがプリン塩基の生合成を阻害する

本剤は、細胞増殖に重要な意義をもつ核酸の生合成を阻害する。メルカプトプリンは細胞内でinosinic acidのチオ同族体 thioinosinic acid（TIMP）に変換し、このTIMPは主としてinosinic acid からのadenylosuccinic acid 及びxanthylic acidへの転換を阻害し、adenine, guanineribonucleotideの生合成を阻害するとされている

適応

急性白血病、慢性骨髄性白血病

白血病、悪性リンパ腫以外の腫瘍に対しては効果が少なく適応されない

注意

アロプリノールと相互作用がある　→代謝抑制

重大な副作用

骨髄抑制

添付文書

ロイケリン散10％

http://www.info.pmda.go.jp/go/pack/4221001B1052_1_02/4221001B1052_1_02?view=body

「イノシン酸」

　　[★]

英: inosinic acid、inosinate
関: イノシン一リン酸

「inosinate」

　　[★]

イノシン酸

関: inosinic acid

[pmid_22531138-1] Davies O, Mendes P, Smallbone K, Malys N (2012). "Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism". BMB Reports 45 (4): 259–64. doi:10.5483/BMBRep.2012.45.4.259. PMID 22531138.

[2] Voet, D, Voet, J. G., Biochemistry (3rd Edition), John Wiley & Sons, Inc., 2004, pg 1095

匿名

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案内

案内

inosinic acid